Organosiloxanes containing ester derivatives of ascorbic acid

ABSTRACT

Organosiloxanes containing ester derivatives of ascorbic acid are disclosed having the formula (R 3 SiO) n R (3-n) Si—X-A wherein R is an alkyl group containing 1 to 6 carbon atoms, n is 1 to 3 inclusive, X is a divalent organic linking group, A is an ester derivative of ascorbic acid. A method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method are also taught. The compounds and compositions of the present disclosure are useful to affect tissue lightening when applied topically to keratinaceous tissue.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 12/680,407 which was a national stage filing under 35 U.S.C. §371 ofPCT Application No. PCT/US08/76494 filed on Sep. 1, 2008 which claimedthe benefit of U.S. Provisional Patent Application No. 60/975,863 filedSep. 28, 2007 under 35 U.S.C. §119(e). U.S. application Ser. No.12/680,407, PCT Application No. PCT/US08/76494 and U.S. ProvisionalPatent Application No. 60/975,863 are hereby incorporated by reference.

TECHNICAL FIELD

This disclosure relates to organosiloxanes having the formula(R₃SiO)_(n)R_((3-n))Si—X-A wherein R is an alkyl group containing 1 to 6carbon atoms, n is 1 to 3 inclusive, X is a divalent organic linkinggroup, and A is an ester derivative of ascorbic acid. This disclosurefurther relates to a method of making an organosiloxane containing esterderivatives of ascorbic acid and the products prepared according to themethod. The compounds and compositions of the present disclosure areuseful to affect tissue lightening when applied topically tokeratinaceous tissue.

BACKGROUND

Ascorbic acid and related compounds are of known utility inskin-lightening and other technologies related to hyper-pigmentation.Ascorbic acid formulations, however, are prone to oxidation and areeasily destabilized. In addition, cosmetic or pharmacologicalcompositions comprising these acids may damage tissue or irritate humanskin on repeated topical applications due to lower pH of theformulations. Hence, ascorbic acid and other related compounds have beencompounded with other hydrophobic materials to improve their stabilityand performance. Most recently, ester derivatives of ascorbic acid and2-keto-acid saccharides have been disclosed in WO 2006/066227 whereinthe ester is introduced by ester bond formation between at least onehydroxy-functionality on the ascorbic acid or 2-keto-acid saccharide anda carboxy-functional organosiloxane. The organosiloxane structuressuggested in WO 2006/066227 are numerous. However, the working examplesin WO 2006/066227 emphasized A-B-A structures based on a linearpolydimethylsiloxane having end groups containing an ester linkage toascorbic acid. While the examples in WO 2006/066227 demonstrated skinlightening effects and good formulation stabilities, they did notprovide skin lightening effects equivalent or better than kojic acid.Kojic acid is known for its skin lightening capabilities and is oftenused as a benchmark for determining skin lightening performance.However, kojic acid's water solubility can limit its delivery andformulation latitude. Furthermore, the use of kojic acid in skin careformulation is questioned in some countries for safety reasons.

The present inventors have unexpectedly discovered certain short chainorganosiloxanes containing ester derivatives of ascorbic acid provideenhanced skin lightening performance. In particular, these ascorbylcontaining short chain organosiloxanes have skin lightening performancecomparable to or better than kojic acid. Furthermore, the presentascorbyl containing short chain organosiloxanes are useful in manypersonal care formulations because of their compatibility with manyorganic oils and silicones.

SUMMARY

This disclosure relates to compounds having the formula

(R₃SiO)_(n)R_((3-n))Si—X-A wherein

-   -   R is an alkyl group containing 1 to 6 carbon atoms,    -   n is 1 to 3 inclusive,    -   X is a divalent organic linking group,    -   A is an ester derivative of ascorbic acid.

This disclosure further provides a method of making an organosiloxanecontaining ester derivatives of ascorbic acid and the products preparedaccording to the method, the method comprising:

-   -   I) providing a protected ascorbic acid by forming a protecting        group from at least one hydroxy-functional group thereon;    -   II) mixing the protected ascorbic acid with a carboxy-functional        organosiloxane having the formula        (R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹        -   where R is an alkyl group containing 1 to 6 carbon atoms,            -   n is 1 to 3 inclusive, X is a divalent organic linking                group,            -   R¹ is a hydrocarbyl containing 1 to 20 carbon atoms or                hydrogen, to form a solution;    -   III) contacting the solution with a biocatalyst which is capable        of catalyzing ester bond formation;    -   IV) optionally, removing the protecting group, and wherein the        protecting group may comprise a functional group.

This disclosure further relates to compositions comprising the presentorganosiloxane compounds and a carrier fluid.

When the compounds and compositions of the present disclosure areapplied topically to keratinaceous tissue, and in particular human skin,tissue lightening effects are effected.

This disclosure yet further relates to keratinaceous tissue lighteningagent compositions comprising the compound and compositions describedherein.

This disclosure yet further relates to personal care compositionscontaining the compounds and compositions described herein.

DETAILED DESCRIPTION

This disclosure relates to organosiloxane compounds having the formula

(R₃SiO)_(n)R_((3-n))Si—X-A wherein

-   -   R is an alkyl group containing 1 to 6 carbon atoms,    -   n is 1 to 3 inclusive, alternatively n is 2.    -   X is a divalent organic linking group, and    -   A is an ester derivative of ascorbic acid.        R may be any alkyl group containing 1 to 6 carbons such as        methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, or        hexyl. Alternatively, R is methyl.

X is a divalent organic linking group. While X may be any organiclinking group, typically X contains 1 to 30 carbon atoms. X may be alinear or branched C₁-C₃₀ alkylene chain. Thus X may be a divalent,aliphatic hydrocarbon group having 1-30 carbons, alternatively having3-12 carbons, or alternatively having 10 carbons such as —(CH₂)₁₀—.

A is an ester derivative of ascorbic acid. The scope of the inventivecompounds includes all ester derivatives of ascorbic acid andisoascorbic acid wherein the organosiloxane is covalently bound to theascorbic, or isoascorbic via an ester bond. As used herein the term“ascorbic acid” includes ascorbic acid and its diastereoisomer,isoascorbic acid, unless specifically referred to as L-ascorbic acid orD-eiythorbic acid, and salts thereof. The fourth and fifth carbon atomsof an ascorbic acid molecule are chiral, leading to the existence of twoenantiomeric isomers at each chiral center for a total of 4diasteroisomers. One of the enantiomers of isoascorbic acid is alsoknown as D-erythorbic acid. Due to its strong reducing properties,D-erythorbic acid has similar technological applications to L-ascorbicacid as a water-soluble antioxidant. “Ascorbic acid” also includes thederivatives of all distereoisomers, including those wherein one or moreof the free hydroxy functional groups thereof are formed as esters,ethers, ketones, and so forth, and including those comprising groupsintended to be protecting and/or functional groups.

In the (R₃SiO)_(n)R_((3-n))Si—X-A formula, A may have the followingstructure;

where each P is independently any protecting or functional group, aproton or a cation chosen from the alkali or alkaline earth metals. Asused herein the term “protecting group” includes groups formed involvingone or more of the free hydroxy functional groups of the ascorbic acid,and includes esters, ethers, ketones and so forth. In one embodiment,the process to form the ester derivative comprises “protecting” at leastone of the hydroxyl groups of the ascorbic acid or derivatives thereofas esters (for example, as acetate esters) or ethers (for example,methyl ethers or), epoxys, or cyclic ketals. In a specific embodimentthe ascorbic acid is protected at one or more hydroxyl sites by initialconversion to the cyclic ketal by the formation of2,3-isopropylidene-ascorbic acid. Also as used herein the term“protecting” group may include a functional group, or addedfunctionality may not relate to “protecting” at all. In one embodiment,the ascorbic acid comprises at least one hydroxy group which isfunctionalized or protected or both.

In another specific embodiment, the ascorbic acid is protected at one ormore hydroxyl sites as esters (for example as O-carbonates, O-acetates,O-phosphates and the like). The latter may then be derivatized usingbiocatalyzed esterification methods described below ultimately toproduce the structures of the present disclosure. In addition, theformation of mono and diphosphates of ascorbic acid are describedthoroughly in the literature. For example, U.S. Pat. No. 4,939,128 toKato et al., the contents of which are incorporated herein by reference,teaches the formation of phosphoric acid esters of ascorbic acid.Similarly, U.S. Pat. No. 4,999,437 to Dobler et al., the contents ofwhich are also fully incorporated herein by reference, describes thepreparation of ascorbic acid 2-phosphate. In another specific embodimentthe ascorbic acid is protected at the hydroxyls by formation of ethers,and in a very specific embodiment the protecting moiety is atrimethylsilyl ether. Any of these known ascorbic acid derivatives canbe used within the scope of the present invention.

In one very specific embodiment, the organosiloxane compound has theformula;

referred herein as “AUTS”.

The process or method of making the organosiloxanes containing esterderivatives of ascorbic acid as described above may vary. Alternatively,they may be prepared by methods as described herein. Thus, the presentdisclosure further provides a method of making organosiloxanescontaining ester derivatives of ascorbic acid comprising:

-   -   I) providing a protected ascorbic acid by forming a protecting        group from at least one hydroxy-functional group thereon;    -   II) mixing the protected ascorbic acid with a carboxy-functional        organosiloxane having the formula        (R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹        -   where R, n and X are the same as described above, and            -   R¹ is a hydrocarbyl containing 1 to 20 carbon atoms or                hydrogen, to form a solution;    -   III) contacting the solution with a biocatalyst which is capable        of catalyzing ester bond formation;    -   IV) optionally, removing the protecting group, and wherein the        protecting group may comprise a functional group.

Step I) of the method provides a protected ascorbic acid by forming aprotecting group from at least one hydroxy-functional group thereon. Theprotecting groups are the same as described above. In a specificembodiment the hydroxyls are protected in the form of a trimethylsilyl(TMS) ether, and in a very specific embodiment the protected ascorbicacid comprises a tetra-O-trimethylsilyl ascorbic acid. Protection as atetra-O-trimethylsilyl derivative allows enhanced miscibility of theascorbic acid with the carboxy-functional organosiloxane. Protection asa tetra-O-trimethylsilyl derivative also allows the removal of the6-O-TMS ether in situ through the action of the carboxy-functionalsiloxane, an additive such as a tertiary alcohol or water generated as aresult of the esterification reaction. The latter also prevents theaccumulation of water during the course of the reaction. Removal of the6-O-TMS ether allows subsequent esterification of the 6-OH group of theotherwise protected ascorbic acid.

In this embodiment, ascorbic acid is reacted with1,1,1,3,3,3-hexamethyldisilazane, typically in a suitable solvent likeacetonitrile, as represented below.

Step II) of the method involves mixing the protected ascorbic acid witha carboxy-functional organosiloxane having the formula(R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹ where R, n and X are the same asdescribed above, and R¹ is a hydrocarbyl containing 1 to 20 carbon atomsor hydrogen, to form a solution. The carboxy-functional organosiloxanehaving the formula (R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹ may be prepared byany method known in the art. Typically, the carboxy-functionorganosiloxanes having the formula (R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹ areprepared by a hydrosilylation reaction between an organohydrogensiloxaneof the average formula (R₃SiO)_(n)R_((3-n))Si—H, where R and n is asdefined above, and a terminally aliphatic unsaturated carboxylic acid orester. Techniques and catalysts for effecting hydrosilylation reactionsare known in the art and any may be used to prepare thecarboxy-functional organosiloxane useful in step II) of the presentmethod. The terminally aliphatic unsaturated carboxylic acid or estermay have the formula R²—Y—R¹ where R² is an monovalent unsaturatedaliphatic hydrocarbon group, Y is a divalent hydrocarbon group, and R¹is as defined above. Typically R² is CH₂═CH—, CH₂═CHCH₂—, or CH≡C—, andsimilar substituted unsaturated groups such as H₂C═C(CH₃)—, andHC≡C(CH₃)—. In one embodiment, the terminally aliphatic unsaturatedcarboxylic acid or ester is an undeconate ester, such as methyl10-undecenoate or ethyl 10-undecenoate. A representative reaction schemeis shown below for producing a carboxy-functional organosiloxane usefulin step II) of the method.

Step III) of the method involves contacting the solution with abiocatalyst which is capable of catalyzing ester bond formation. As usedherein, the term “biocatalyst” includes: 1) natural, semi-synthetic, ormetabolically engineered catalytic substances that are isolated frombiological sources; and 2) synthetic catalytic molecules that mimicbiological pathways. As used herein, the term “enzyme” includes proteinsthat are capable of catalyzing chemical changes in other substances. Theenzymes can be wild-type enzymes or variant enzymes. Enzymes within thescope of the present invention include, but are not limited to,pullulanases, proteases, cellulases, amylases, isomerases, lipases,oxidases, oxidoreductases, hydrolases, aldolases, ketolases,glycosidases, oxidoreductases, hydrolases, aldolases, ketolases,glycosidases, lyases, ligases, transferases, and ligases.

As used herein, the term “lipolytic enzyme” refers to a polypeptide,protein or enzyme exhibiting a lipid degrading capability such as acapability of degrading a triglyceride or a phospholipid. A lipolyticenzyme may be, for example, a lipase, a phospholipase, an esterase or acutinase. For the present invention, lipolytic activity may bedetermined according to any procedure known in the art. See, forexample, Gupta et al, Biotechnol. Appl. Biochem. (2003) 37:63-71; Andre,Christophe, et al, U.S. Pat. No. 5,990,069 (International Publication WO96/1 8729A1). As used herein, the term “protein” refers to polymers oflarge molecular mass composed of one or more polypeptide chains andwhose monomers are amino acids joined together by peptide bonds. Theterms “protein” and “polypeptide” are sometimes used interchangeablyherein. The conventional one-letter or three-letter code for amino acidresidues is used herein.

In a specific embodiment the biocatalyst comprises an enzyme, and in amore specific embodiment the biocatalyst comprises a hydrolase enzyme.In very specific embodiments the hydrolase enzyme is selected from thegroup consisting of a lipase, a protease, a phosphoesterase, anesterase, an amidase, a cutinase, and combinations thereof. In an evenmore specific embodiment the hydrolase enzyme comprises a lipase, and ina further specific embodiment the lipase comprises an immobilized formof Candida antarctica lipase B (CALB) marketed as N435 and availablefrom Novozymes (Denmark).

Step III is typically performed under those conditions that favor theformation of ester bonds such as the removal or sequestration of wateror low molecular weight alcohols to prevent the hydrolysis of the esterfunctionalities.

One of ordinary skill in the art will appreciate that additionalsynthetic methods could be used to produce the aforementioned compounds.For example, the linker group could be attached to ascorbic acid throughester bond formation, and subsequently the modified linker may beattached to an organosiloxane polymer comprising an appropriatechemistry. In one specific example, an ascorbic acid-modified linkerbearing a terminal olefinic function could be attached to ahydride-functional organosiloxane via hydrosilylation. Alternatively,the ester linkage may result from the reaction of an organosiloxanecontaining an acid chloride, such as 10-undecenoyl chloride, withascorbic acid.

The present disclosure further provides compositions containing theorganosiloxane compounds as described above and a carrier fluid. Thecarrier fluid may be either an organic or silicone fluid. Suitablecarrier fluids include silicones, both linear and cyclic, organic oils,organic solvents and mixtures of these. Specific examples of solventsmay be found in U.S. Pat. No. 6,200,581, which is hereby incorporated byreference for this purpose.

Typically, the carrier fluid is a low viscosity silicone or a volatilemethyl siloxane or a volatile ethyl siloxane or a volatile methyl ethylsiloxane having a viscosity at 25° C. in the range of 1 to 1,000 mm²/secsuch as hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane,decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane,octamethyltrisiloxane, decamethyltetrasiloxane,dodecamethylpentasiloxane, tetradecamethylhexasiloxane,hexadeamethylheptasiloxane,heptamethyl-3-{(trimethylsilyl)oxy)}trisiloxane,hexamethyl-3,3,bis{(trimethylsilyl)oxy}trisiloxanepentamethyl{(trimethylsilyl)oxy}cyclotrisiloxane as well aspolydimethylsiloxanes, polyethylsiloxanes, polymethylethylsiloxanes,polymethylphenylsiloxanes, polydiphenylsiloxanes.

Organic solvents may be exemplified by, but not limited to, aromatichydrocarbons, aliphatic hydrocarbons, alcohols, aldehydes, ketones,amines, esters, ethers, glycols, glycol ethers, alkyl halides andaromatic halides. Hydrocarbons including isododecane, isohexadecane,Isopar L (C11-C13), Isopar H (C11-C12), hydrogentated polydecene. Ethersand esters including isodecyl neopentanoate, neopentylglycol heptanoate,glycol distearate, dicaprylyl carbonate, diethylhexyl carbonate,propylene glycol n butyl ether, ethyl-3 ethoxypropionate, propyleneglycol methyl ether acetate, tridecyl neopentanoate, propylene glycolmethylether acetate (PGMEA), propylene glycol methylether (PGME),octyldodecyl neopentanoate, diisobutyl adipate, diisopropyl adipate,propylene glycol dicaprylate/dicaprate, and octyl palmitate. Additionalorganic carrier fluids suitable as a stand alone compound or as aningredient to the carrier fluid include fats, oils, fatty acids, andfatty alcohols.

The amount of organosiloxane compounds combined with the carrier fluidmay vary, such as from 0.1 wt % to 99 wt % percent of the organosiloxanein the carrier fluid.

Formulations containing organosiloxanes containing ester derivatives ofascorbic acid are contemplated for use in skin-lightening products. Forexample an emulsion of an organosiloxane containing ester derivatives ofascorbic acid and water containing 0.1 to 50% active ascorbic acid isapplied to skin over a period of time to lighten the tone of the skinand remove blemishes and other discolorations. The active ascorbic acidin the said formulations can be that either covalently bound tocarboxy-functional polysiloxanes, as well as free unconjugated ascorbicacid and mixtures thereof. Such formulations may optionally containadditional active compounds including vitamins, fragrances,anti-oxidants, herbal extracts, surfactants, humectants and the like.

One particular embodiment is directed to a keratinaceous tissuelightening agent comprising the inventive ester derivatives of eitherascorbic acid. In a specific embodiment the keratinaceous tissuecomprises human skin. A further embodiment provides a compositioncomprising a safe and effective amount of the keratinaceous tissuelightening agent and a suitable vehicle or base. In a more specificembodiment the composition is in the form of an emulsion. In one aspectof these embodiments, the novel compound comprises the inventiveorganosiloxanes containing ester derivatives of ascorbic acid and iscontemplated as a controlled release keratinaceous tissue lighteningagent.

A further embodiment provides a method of lightening keratinaceoustissue comprising topical application of the compositions comprising theinventive ester derivatives of ascorbic acid. One particular embodimentprovides a method of lightening keratinaceous tissue comprising topicalapplication of a controlled release composition which comprises theorganosiloxanes containing ester derivatives of ascorbic acid. Such“controlled release,” for example, may be achieved by delivery of aprecursor which allows sustained release of ascorbic acid or undergoessubsequent conversion to free ascorbic acid. In a very specificembodiment the controlled release composition comprises inventiveorganosiloxanes containing ester derivatives of ascorbic acid.

Other embodiments are directed to personal care formulations comprisingcosmetic or personal care compositions. Since the inventiveorganosiloxanes containing ester derivatives of ascorbic acid exhibit arelatively-higher permeability to the skin and mucosa, they aredesirable for cosmetic applications which generally include skin, hair,and orally-usable products. The inventive ester derivatives may also bemixed with other cosmetically suitable ingredients such as oily bases,water-soluble bases, flavors, colors, dyes, refrigerants, humectants,emollients, emulsifiers, gelation agents, viscosity enhancers,surfactants, stabilizers for foaming, clearances, antioxidants,germicides, putrefactive agents, coating-forming agents, and injectionagents. The cosmetics according to the present invention contain atleast 0.1 w/w %, and preferably at least 1.0 w/w % of the presentinventive ester derivatives. It is also contemplated that the inventiveester derivatives may provide skin absorption enhancing effects to otherbenefit agents intended to provide benefit via absorption through theskin when administered in conjunction with those benefit agents. Theinventive ester derivatives may also be desirably mixed with one or morepharmaceutical or nutritive agents such as vitamins, amino acids,peptides, hormones, extracts, vasodilators, blood circulation-promotingagents, cell-activating agents, anti-inflammatory drugs,urtication-preventing agents, skin-function-promoting agents, enzymes,and keratolytics. The mixtures may be in the form of liquid, emulsion,cream, paste, powder, granule, or solid products. The personal carecompositions according to the present invention contain at least 0.1 w/w%, and preferably at least 1.0 w/w % of the present inventive esterderivatives.

Also contemplated are formulations with minimal water content where anorganosiloxane containing ester derivative of ascorbic acid isformulated with additional polysiloxane materials includingpolydimethylsiloxane, polydimethylsiloxane polyethers, siloxane resinsand other organosiloxane compounds. Such formulations may also containadditional active compounds including vitamins, fragrances,anti-oxidants, herbal extracts and the like.

EXAMPLES

These examples are intended to illustrate the invention to one ofordinary skill in the art and should not be interpreted as limiting thescope of the invention set forth in the claims. All measurements andexperiments were conducted at 23° C., unless indicated otherwise.

Example 1 Preparation of Trisiloxane-Undecyl Methyl Ester Run 1A

1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,329 g, 6.0 moles) and methyl10-undecenoate (1,421.0 g, 7.2 moles) were placed in a 5000 mL threeneck flask. The mixture was heated to 80° C. and 1.4 mL of a 1.0 weightpercent chloroplatinic acid solution in 2-propanol was added (finalplatinum content is 4 ppm). The temperature of the mixture was thenmaintained at 100° C. for 24 hours. Measurement of the SiH contentindicated that the reaction had proceeded to 98% completion. The excessmethyl 10-undecenoate and other volatiles were removed by heating themixture to 105° C./1 mmHg. Characterization of the product by FTIR, GC,¹³C NMR and ²⁹Si NMR indicated that the desired material was obtained asa slightly tan liquid.

Run 1B

1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,208.2 g, 5.4 moles) was placedin a 5000 mL three neck flask. An addition funnel was charged withmethyl 10-undecenoate (1,291.9 g, 6.5 moles). The content of the pot washeated to 75° C. and a small amount of methyl 10-undecenoate wasintroduced just prior to adding 0.45 mL of a 2.67 weight percent Pt IVsolution (final Pt content of 4 ppm). The methyl 10-undecenoate wasadded from the addition funnel at a rate so the temperature of thereaction did not exceed 100° C. After the addition of the methyl10-undecenoate was complete the mixture was maintained at 90° C. for 12hours. The reaction was determined to be 98% complete based on theconsumption of SiH. The crude reaction mixture was heated to 95° C./1mmHg to remove volatiles and excess methyl 10-undecenoate from theproduct. Characterization of the product (GC, FTIR, ¹³C NMR and ²⁹SiNMR) confirmed that the desired product had been obtained as a slightlytan liquid.

Run 1C

1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,691.5 g, 7.6 moles) was placedin a 5000 mL three neck flask. An addition funnel was charged withmethyl 10-undecenoate (1,000.1 g, 5.0 moles) which had been distilled at71-74° C./1 mmHg prior to use. The content of the pot was heated to 70°C. and a small amount of methyl 10-undecenoate was introduced just priorto adding 0.60 mL of a 2.67 weight percent Pt IV solution (final Ptcontent of 4 ppm). The methyl 10-undecenoate was added from the additionfunnel at a rate so the temperature of the reaction did not exceed 90°C. After the first amount of methyl 10-undecenoate had been added andadditional 808.5 g (4.1 moles) was added via the addition funnel. Afterall the methyl 10-undecenoate had been added the mixture was maintainedat 75° C. for 1 hour at which point FTIR indicated that 99.5% conversionhad been achieved based on SiH consumption. Volatiles and excess methyl10-undecenoate were removed from the crude product mixture by to 90°C./1 mmHg. The pressure in the reaction flask was brought to atmosphericand 50 g of activated carbon was introduced. The mixture was maintainedat 90° C. for 6 hours. Next, the mixture was filtered through Celite toobtain the product as a colorless liquid. Characterization (GC, FTIR,¹³C NMR and ²⁹Si NMR) indicated that the desired product had beenobtained. Additionally, ICP analysis indicated that the level ofplatinum in this product was <1 ppm.

Example 2 Preparation of Trisiloxane-Undecyl Ethyl Ester

1,1,1,3,5,5,5-Heptamethyltrisiloxane (116.6 g, 0.52 moles) and ethyl10-undecenoate (133.5 g, 0.63 moles) were placed in a 500 mL three neckflask. The mixture was heated to 80° C. and 60 μl of a 2.67 weightpercent Pt IV solution (final Pt content of 5 ppm) was added. Thetemperature of the mixture was then maintained at 100° C. for 6 hours.Measurement of the SiH content indicated that the reaction had proceededto 98.5% completion. The excess ethyl 10-undecenoate and other volatileswere removed by heating the mixture to 105° C./1 mmHg. Characterizationof the product by FTIR, GC, ¹³C NMR and ²⁹Si NMR indicated that thedesired material was obtained as a slightly tan liquid.

Example 3 Preparation of Trimethylsilyl-Functional Ascorbic Acid

Acetonitrile (1883.5 grams) was added into a 5000 mL three neck roundbottom-jacketed flask. The flask was connected to a circulating waterbath, containing an antifreeze/water solution, with a set pointtemperature of 0° C. A small vent was placed in the side neck of theflask. The flask was purged and then a Nitrogen sweep was appliedthroughout the reaction to remove any ammonia generated during thecapping process. L-Ascorbic Acid (536.0 grams, 1.11 moles) was slowlyadded to the acetonitrile with rapid mixing using a mechanical stirrerwith a Teflon stir rod and paddle. 1,1,1,3,3,3-Hexamethyldisilazane(1109.3 grams, 2.54 moles) was added to this mixture with rapid mixing.Mixing at 0° C. was maintained overnight. The mixture was then allowedto equilibrate to room temperature with mixing for two additional hours.The reaction mixture was transferred into single neck round bottomrecovery flasks and concentrated under vacuum at 35-50° C. using aRotavapor. A clear solution formed, which was poured into amber bottles,purged with nitrogen and placed into a 4° C. refrigerator for storage.

Example 4 Preparation of Ascorbyl Undecyl Trisiloxane (AUTS)

The trimethylsilyl-functional ascorbic acid of Example 3 (201.4 grams,0.43 moles) and distilled-trisiloxane undecyl methyl ester of Example 1(190.5 grams, 0.43 moles) were added into a 600 mL water-jacketedreaction flask that was connected to a circulating water bath with a setpoint temperature of 70° C. A nitrogen sweep was applied to the flaskand a small vent was placed in one of the flask necks to remove anymethanol formed during the reaction. A lipase enzyme immobilized on apolyacrylic resin bead (39.22 grams) and t-amyl alcohol (47.84 grams)were added to the flask with rapid mixing. The reaction mixture wasmixed for 87.5 hours and then drained from the reactor into a2000-milliliter single-neck round-bottom flask. Methanol (407.7 grams)was added to the flask, capped flask and mixed at room temperature fortwo hours on a Rotavapor without the use of vacuum. Filtered solidparticles from the flask using a number five Whatman filter paper in aBuchner funnel with vacuum. Methanol was than stripped from the productunder vacuum using a Rotavapor set to 65° C. until a viscousstraw-colored fluid was remaining. Acetone (230.2 grams) was added tothe reaction product and was mixed on a Rotavapor without the use ofvacuum until the entire product was in a solution with the acetone.Solution was centrifuged at 3500 rpm to separate any unreacted ascorbicacid from the product. The liquid phase was recovered and centrifugedagain. This process was repeated until there was no visually apparentresidue present in the solution. The acetone was then removed by avacuum strip on a Rotavapor at 68° C. Product was a clear, viscous,amber/straw-colored fluid.

Example 5

Preparation of Ascorbyl Undecyl Trisiloxane (from Ethyl Ester)

The trimethylsilyl-functional ascorbic acid of Example 3 (15.0 grams,0.32 moles) and trisiloxane undecyl ethyl ester of Example 2 (13.6grams, 0.32 moles) were added into a 50 mL water-jacketed reaction flaskthat was connected to a circulating water bath with a set pointtemperature of 70° C. A Nitrogen sweep was applied to the flask and asmall vent was placed in one of the flask necks to remove any methanolformed during the reaction. A lipase enzyme immobilized on a polyacrylicresin bead (3.2 grams) and t-Amyl Alcohol (3.9 grams) was added to theflask with rapid mixing. The reaction mixture was mixed for 72 hours andthen drained from the reactor into a 50-milliliter centrifuge tube. Thetube was centrifuged at 4000 rpm to separate any un-reacted ascorbicacid from the product. The liquid phase was recovered and centrifugedagain. This process was repeated until there was no visually apparentresidue present in the solution. The capped product was a viscous,amber/straw-colored fluid.

Example 6

Preparation of Ascorbyl Undecyl Trisiloxane (AUTS) using a RecycleProcess

The trimethylsilyl-functional ascorbic acid of Example 3 (354.5 grams,0.73 moles), trisiloxane undecyl methyl ester of Example 1 (320.9 grams,0.73 moles) and cyclopentasiloxane (386.8 grams) were added into a 2000mL water-jacketed reaction flask that was connected to a circulatingwater bath with a set point temperature of 70° C. A Nitrogen sweep wasapplied to the flask and a small vent was placed in one of the flasknecks to remove any methanol formed during the reaction. The flask drainwas plumbed using a glass adapter to attach ⅛ inch inside diameterTeflon tubing using compression fittings. The tubing was attached to thetop of a one-inch diameter, water-jacketed column with a total length of300 mL. The column was packed, from bottom to top, with a coarse diskfilter, glass beads (35.0 grams) and a lipase enzyme immobilized on apolyacrylic resin bead (65.1 grams). Tubing was attached to the columnoutlet and run back to the original reaction flask. The reaction mixturewas stirred slowly using a mechanical stirrer with a Teflon stir rod andpaddle. This mixture was pumped from the flask bottom through tubing,pressure relief valve, pressure gauge, into the top of the column,through the bottom of the column and then pumped back into the flask.The reaction mixture was mixed/pumped for 124.5 hours and then drainedfrom the reactor into a 3000-milliliter single-neck round-bottom flask.Methanol (684.7 grams) was added to the flask, capped flask and mixed atroom temperature for two hours on a Rotavapor without the use of vacuum.Methanol was than stripped from the product under vacuum using aRotavapor set to 65° C. until a viscous straw-colored fluid wasremaining. Acetone (700.0 grams) was added to the reaction product andwas mixed on a Rotavapor without the use of vacuum until the entireproduct was in a solution with the acetone. Solution was centrifuged at3500 rpm to separate any unreacted ascorbic acid from the product. Theliquid phase was recovered and centrifuged again. This process wasrepeated until there was no visually apparent residue present in thesolution. The acetone was then removed by a vacuum strip on a Rotavaporat 68° C. Product was a clear, viscous, amber/straw-colored fluid.

Example 7 Thin Film Strip to Purify the Trimethyl Silyl Ether (TMS)Capped Ascorbyl Undecanoate Trisiloxane (AUTS) Product

A reaction product mixture containing trimethylsilyl-functional ascorbicacid (such as from Example 3) was placed in the reservoir of a thin filmstripping apparatus. The external jacket of the apparatus was heated toand maintained at 175±5° C. The vacuum was introduced to the system andallowed to run until the pressure in the system is below 1.5 mmHg. Oncethe temperature and pressure have reached the set values, the productmixture is introduced to the top of the thin film stripper wiper bladesand the motor is now turned on to start the wiper assembly spinning. Thematerial is introduced from the reservoir at such a rate as to notoverwhelm the wiper blades (˜1 ml/min). The volatile components underthese conditions, the trimethyl silyl ether capped ascorbic acid and themethyl 10-undecanoate trisiloxane are volatilized and condense on theinternal cold finger while the purified trimethyl silyl ether cappedascorbyl 10-undecanoate trisiloxane remains in the non-volatile portionof the thin film stripper. Both the non-volatile and volatile portionsof the process are collected. Using this method, it is possible toobtain trimethyl silyl ether capped ascorbyl undecanoate trisiloxanethat contains less than 1% of the trimethyl silyl ether capped ascorbicacid and less than 1% of the methyl 10-undecanoate trisiloxane.

Example 8 A Non-Enzymatic Method to Prepare Ascorbyl 10-UndecanoteTrisiloxane

To a 50 ml three neck round bottom flask was added 5.0 g (28.4 mmoles)of ascorbic acid, 4.7 ml (3.4 g, 34.0 mmoles) of triethylamine and 30 mlof N,N,-dimethylformamide. To this mixture was slowly added, withstirring, 7.0 g (34.5 mmoles) of 10-undecenoyl chloride. During theaddition, a slight exotherm was observed. The mixture was allowed tostir for 2.5 h and then filtered to remove the precipitate that hadformed. The filtrate was diluted with toluene, placed in a separatoryfunnel and washed with 2×100 ml portions of water, 2×100 ml portions ofsaturated sodium bicarbonate, 2×100 ml portions of water and then 1×100ml portion of saturated sodium chloride. The organic layer was driedover anhydrous magnesium sulfate, filtered and the solvent removed on arotary evaporator to yield a slightly yellow oil.

Example 9

Skin Lightening with Ascorbyl Undecyl Trisiloxane (AUTS)

This example illustrates cell viability properties and efficacy of skinlightening formulations according to the present invention. Inparticular, two formulations according to the present invention(containing AUTS as prepared according to Example 4), water (a negativecontrol), 1% kojic acid (Sigma, WI) in water (positive control), andascorbyl tetraisopalmitate in D5 (decamethylcyclopentasiloxane) wereassayed and compared for cell viability and skin lightening efficacy(see Table 1)

TABLE 1 Preparations assayed and cell viability by MTT Viability byCompound Carrier Concentration¹ Dosed MTT AUTS D5 3.2% 10 μL 95.5% AUTSD5 3.2% 25 μL 96.5% VC-IP D5 6.4% 10 μL 94.1% VC-IP D5 6.4% 25 μL 98.2%Negative control: 25 μL water Positive control: 25 μL kojic acid, 1%

-   Test Preparation: 3.2 wt % AUTS in decamethylcyclopentasiloxane    (D5).-   Reference Preparation: 6.4% Nikkol VC-IP (ascorbyl tetraisopalmitate    supplied by Nikko Chemicals Co, Ltd. Of Japan) in D5-   ¹The concentrations of the test material and the reference material    were set to provide the equivalent of 1% ascorbic acid in the test    solutions.

MELANODERM™ cell viability was tested by MTT assay after exposure totest and reference preparations. The assays were carried out usingMelanoderm tissue model MEL 300 A cell line (MELANODERM tissue modelavailable from MatTek, Ashland, Mass.). This melanoderm model consistsof normal, human-derived epidermal keratinocytes and melanocytes thathave been co-cultured to form a multilayer, highly differentiated modelof human epidermis. MTT data showed that viability of MelanoDerm skinmodel was not affected by the treatment. (Cell viability with bothmaterials in D5 at 10 and 25 μL dose was >90%).

Skin whitening effect was evaluated by measuring melanin concentration(μg/ml) after six applications of each preparation. The results aresummarized in Table 2.

TABLE 2 Melanin concentration at Day 10 Test Preparation vs ReferencePreparation AUTS, VC-IP, AUTS, VC-IP, Kojic Acid*** 10 μl 10 μl 25 μl 25μl 25 μL Average 37.4* 57.8* 26.6** 55.2** 41.9 (μg/ml) SD 7.5 3.8 4.45.9 P value 1.1E−03 7.3E−05 *Significantly lower melanin concentration(p < 0.05) in cell culture dosed with AUTS, 10 μl in comparison withVC-IP, 10 μl. **Significantly lower melanin concentration (p < 0.05) incell culture dosed with AUTS, 25 μl in comparison with VC-IP, 25 μl.***1 wt % in water

Example 9 Comparative Solubility of Ascorbyl Undecyl Trisiloxane (AUTS)in Various Personal Care Solvents

The solubility characteristics of the organosiloxanes containing esterderivatives of ascorbic acid of the present disclosure vs theorganosiloxanes as taught in WO2006/066227 is shown in thisrepresentative comparative example.

A 36 wt % mixture of the referenced sample and listed solvents wereprepared in a glass vial. The sealed glass vials containing the mixtureswere then placed in a 60° C. water bath and periodically shaken andobserved. The results, as summarized in Table 3, show the representativeorganosiloxanes of the present disclosure had improved solubilitycharacteristics.

-   Comparative sample #1 is the same average formula as the ascorbyl    containing organosiloxane of Example 4 in WO2006/066227.-   Comparative sample #2 is the same average formula as the ascorbyl    containing organosiloxane of Example 6 in WO2006/066227.-   AUTS is representative of Example 4 as described above.

TABLE 3 Reference A B C D E Water Bis-Ascorbyl Undecyl Comparative No NoNo No na Yes* Tetramethyldisiloxane sample #1 Bis-Ascorbyl UndecylComparative Yes No No Yes Yes No Polydimethylsiloxane sample #2 AscorbylUndecyl AUTS Yes** Yes** Yes** na Yes** No A = C12-15 Alkyl Benzoate(FINSOLV TN) B = Cyclopentasiloxane (Dow Corning 245 Fluid) C = Squalane(Uniqema PRIPURE 3759) D = Tricaprylin (TRIVENT OC-G) E =Caprylic/Capric Triglyceride *forms a translucent mixture that thickensto a viscous hazy liquid when cooled **dissolves to form a solution thatranges from nearly clear to hazy, depending on the solvent; solutionsgel when cooled to room temperature

Example 10 Personal Care Formulations Containing Ascorbyl UndecylTrisiloxane (AUTS)

Representative ascorbyl undecyl trisiloxanes were incorporated intovarious personal care formulations as illustrated below to demonstrate.

Facial Moisturizer

Weight % INCI name Trade Name (Supplier) Part A 5.0%Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) AcryloyldimethylTaurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8%Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% AscorbylUndecyl Trisiloxane (AUTS) 4.0% Diethylhexyl Succinate Crodamol OSU(CRODA) Part B 2.0% Glycerin 78.8% Deionized Water 0.2% Propylene Glycol(and) Diazolidinyl Liquid Germall Plus Urea (and) Iodopropynyl Carbamate(SUTTON LABS) 100.0%PROCEDURE: Combine the AUTS, cyclopentasiloxane, and diethylhexylsuccinate in a vessel that is large enough to hold the entire batch.Heat these ingredients with gently mixing to about 60° C. until the AUTSdisperses completely. Add the Simulgel FL and mix until uniform whilemaintaining the temperature at about 55° C. Mix the ingredients for PartB in a separate vessel until a homogenous solution is obtained and heatto about 55° C. Slowly add Part B to Part A with continuous mixing. Thebatch will thicken as more of Part B is added. After all of Part B hasbeen added, mix the batch with sufficient agitation to achieve goodturnover and allow the batch to cool to room temperature.Facial Moisturizer with Inorganic Sunscreen

Weight % INCI name Trade Name (Supplier) Part A 5.0%Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) AcryloyldimethylTaurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8%Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% AscorbylUndecyl Trisiloxane (AUTS) 4.0% Titanium Dioxide (and) Alumina UV-TITANM262 (and) Dimethicone (Kemira) 6.0% Dimethicone Dow Corning ® 200Fluid/100 cSt (DOW CORNING) Part B 2.0% Glycerin 72.8% Deionized Water0.2% Propylene Glycol (and) Diazolidinyl Liquid Germall Plus Urea (and)Iodopropynyl Carbamate (SUTTON LABS) 100.0%PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using highshear mixing equipment to fully disperse the titanium dioxide. Set thisdispersion aside. Combine the AUTS and cyclopentasiloxane in a vesselthat is large enough to hold the entire batch. Heat these ingredientswith gently mixing to about 60° C. until the AUTS disperses completely.Add the Simulgel FL and the titanium dioxide dispersion, then mix untiluniform while maintaining the temperature at about 55° C. Mix theingredients for Part B in a separate vessel until a homogenous solutionis obtained and heat to about 55° C. Slowly add Part B to Part A withcontinuous mixing. The batch will thicken as more of Part B is added.After all of Part B has been added, mix the batch with sufficientagitation to achieve good turnover and allow the batch to cool to roomtemperature.Facial Moisturizer with Organic Sunscreen

Weight % INCI name Trade Name (Supplier) Part A 7.5%Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) AcryloyldimethylTaurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8%Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% AscorbylUndecyl Trisiloxane (AUTS) 7.5% Ethylhexyl Methoxycinnamate Escalol 557(Octinoxate) (International Specialty Porducts) Part B 2.0% Glycerin72.8% Deionized Water 0.2% Propylene Glycol (and) Diazolidinyl LiquidGermall Plus Urea (and) Iodopropynyl Carbamate (SUTTON LABS) 100.0%PROCEDURE: Combine the AUTS, cyclopentasiloxane, and ethylhexylmethoxycinnamate in a vessel that is large enough to hold the entirebatch. Heat these ingredients with gently mixing to about 60° C. untilthe AUTS disperses completely. Add the Simulgel FL and mix until uniformwhile maintaining the temperature at about 55° C. Mix the ingredientsfor Part B in a separate vessel until a homogenous solution is obtainedand heat to about 55° C. Slowly add Part B to Part A with continuousmixing. The batch will thicken as more of Part B is added. After all ofPart B has been added, mix the batch with sufficient agitation toachieve good turnover and allow the batch to cool to room temperature.

Anhydrous Sunscreen Ointment

Wt. % INCI name Trade Name (Supplier) 2.0% Titanium Dioxide (and)Alumina UV-TITAN M262 (Kemira) (and) Dimethicone 3.0% Dimethicone DowCorning ® 200 Fluid/ 100 cSt (DOW CORNING) 21.8% Cyclopentasiloxane DowCorning ® 245 Fluid (DOW CORNING) 65.0% Cyclopentasiloxane (and) DowCorning ® 9045 Dimethicone Crosspolymer Silicone Elastomer Blend (DOWCORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 5.0% EthylhexylMethoxycinnamate (Octoxinate) 100.0%PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using highshear mixing equipment to fully disperse the titanium dioxide. Combinethe remaining ingredients in a suitable mixing vessel. Heat theseingredients to about 60° C. and then mix until the AUTS is melted anduniformly dispersed. Begin cooling the batch and add the titaniumdioxide/dimethicone dispersion to the batch. Mix until uniform andcontinue mixing until the batch cools to room temperature.

Water-in-Oil Sunscreen Lotion

Weight % INCI name Trade Name (Supplier) Part A 3.4% Titanium Dioxide(and) Alumina UV-TITAN M262 (and) Dimethicone (Kemira) 6.6% DimethiconeDow Corning ® 200 Fluid/100 cSt (DOW CORNING) 7.5% Cyclopentasiloxane(and) PEG/PPG- Dow Corning ® 5225C 18/18 Dimethicone Formulation Aid(DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 6.8%Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 5.0% AluminumStarch Octenyl Succinate Dry Flo PC/National Starch and Chemical 4.0%Cyclopentasiloxane (and) Dow Corning ® 749 Trimethylsiloxysilicate Fluid(DOW CORNING) Part B 62.3% Water 1.0% Sodium Chloride 0.2% Polysorbate20 Tween 20 (CRODA) 100.0%PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using highshear mixing equipment to fully disperse the titanium dioxide. Combinethe titanium dioxide dispersion with the remaining ingredients for PartA in a mixing vessel that is large enough to contain the entire batch.Heat Part A to about 60° C. and mix until the AUTS is melted anduniformly dispersed. Combine the ingredients for Part B in a separatevessel and mix until a homogeneous solution is obtained, then heat toabout 60° C. Slowly add Part B to Part A while mixing vigorously toproduce a turbulent mixing action such that Part B is quicklyincorporated into the batch as it is added. When all of Part B has beenadded, begin cooling and continue mixing for another 10-15 minutes.

1. A method of making an organosiloxane containing ester derivative ofascorbic acid comprising: I) providing a protected ascorbic acid byforming a protecting group from at least one hydroxy-functional groupthereon; II) mixing the protected ascorbic acid with acarboxy-functional organosiloxane having the formula(R₃SiO)_(n)R_((3-n))Si—X—C(O)OR¹ where R is an alkyl group containing 1to 6 carbon atoms, n is 1 to 3 inclusive, X is a divalent organiclinking group, R¹ is a hydrocarbyl containing 1 to 20 carbon atoms orhydrogen, to form a solution; III) contacting the solution with abiocatalyst which is capable of catalyzing ester bond formation; IV)optionally, removing the protecting group, and wherein the protectinggroup may comprise a functional group.
 2. The method of claim 1 whereinthe protecting group comprises a trimethylsilyl ether.
 3. The method ofclaim 1 wherein the carboxy-functional organosiloxane formula R ismethyl and n=2.
 4. The method of claim 1 wherein the carboxy-functionalorganosiloxane formula X is a linear or branched C₁-C₃₀ alkylene chain.5. The method of claim 1 wherein the carboxy-functional organosiloxaneformula X is —(CH₂)₁₀—.
 6. The method of claim 1 wherein thecarboxy-functional organosiloxane formula R¹ is methyl or ethyl.
 7. Themethod of claim 1 wherein the biocatalyst comprises an enzyme.
 8. Themethod of claim 7 wherein the enzyme comprises a hydrolase enzyme. 9.The method of claim 8 wherein the hydrolase enzyme exits in either freeor immobilized form and is selected from the group consisting of alipase, a protease, a phosphoesterase, an esterase, a cutinase, andcombinations thereof.
 10. The method of claim 8 wherein the hydrolaseenzyme comprises a lipase.
 11. The product produced by the method ofclaim
 1. 12. A keratinaceous tissue lightening agent compositioncomprising the product as claimed in claim
 11. 13. The keratinaceoustissue lightening agent composition of claim 12 wherein thekeratinaceous tissue comprises human skin.
 14. The keratinaceous tissuelightening agent composition of claim 13 further comprising a suitablevehicle or base.
 15. The keratinaceous tissue lightening agentcomposition of claim 14 further comprising free ascorbic acid.
 16. Thekeratinaceous tissue lightening agent composition of claim 14 whereinthe composition is in the form of an emulsion.
 17. A personal carecomposition comprising the product of claim 11.